Lichen planus is a chronic inflammatory disease of unknown etiology involving the skin and/or mucous membranes, leading to a variety of clinical presentations (Le Cleach L, Chosidow O. Clinical practice. Lichen planus. N Engl J Med 2012; 366:723-32). Oral lichen planus (OLP) is the most prevalent subtype in this latter entity, affecting 0.1 to 4% of the general population, and is characterized by a severely disabling course in its ulcerative form, which often require immunomodulatory systemic therapies such as oral steroids, immunosuppressants and more recently extracorporeal photochemotherapy (ECP)(Edwards P C, Kelsch R. Oral lichen planus: clinical presentation and management. J Can Dent Assoc 2002; 68:494-9; Guyot A D, Farhi D, Ingen-Housz-Oro S, et al. Treatment of refractory erosive oral lichen planus with extracorporeal photochemotherapy: 12 cases. The British journal of dermatology 2007; 156:553-6; Becherel P A, Bussel A, Chosidow O, Rabian C, Piette J C, Frances C. Extracorporeal photochemotherapy for chronic erosive lichen planus. Lancet 1998; 351:805).
OLP is a chronic, disabling muco-cutaneous dys-immune rare disease characterized by mucosal inflammatory erosive lesions with pathological evidence for a marked CD8+ cytotoxic T-cell (CTL) infiltration. Pathologically, OLP is characterized by a predominant infiltrate of immune cells, mainly CD8+ cytotoxic T-lymphocytes (CTLs), associated with apoptosis of epithelial cells and disruption of the basement membrane zone (Zhou X J, Sugerman P B, Savage N W, Walsh L J, Seymour G J. Intra-epithelial CD8+ T cells and basement membrane disruption in oral lichen planus. J Oral Pathol Med 2002; 31:23-7). Likewise, the presence in OLP lesions of activated CTLs in the vicinity of damaged epithelial cells, supports the hypothesis that a dys-regulated cytotoxic T-cell response of unknown antigen specificity plays a key role in the pathogenesis of the disease (Santoro A, Majorana A, Bardellini E, et al. Cytotoxic molecule expression and epithelial cell apoptosis in oral and cutaneous lichen planus. Am J Clin Pathol 2004; 121:758-64).
However, the nature of these antigens remains controversial. Indeed, while autoreactivity of lesional skin-derived CTLs against epithelial cells has been suggested by studies in OLP patients (Sugerman P B, Satterwhite K, Bigby M. Autocytotoxic T-cell clones in lichen planus. The British journal of dermatology 2000; 142:449-56), several studies identified the presence of DNA from several Human Papilloma Virus (HPV) subtypes including HPV16 and HPV18 in mucosal lesions of OLP, raising the issue of the self versus non-self (HPV) nature of target antigens in OLP, two non-mutually exclusive hypotheses (Jontell M, Watts S, Wallstrom M, Levin L, Sloberg K. Human papilloma virus in erosive oral lichen planus. J Oral Pathol Med 1990; 19:273-7; Young S K, Min K W. In situ DNA hybridization analysis of oral papillomas, leukoplakias, and carcinomas for human papillomavirus. Oral surgery, oral medicine, and oral pathology 1991; 71:726-9; Lodi G, Scully C, Carrozzo M, Griffiths M, Sugerman P B, Thongprasom K. Current controversies in oral lichen planus: report of an international consensus meeting. Part 1. Viral infections and etiopathogenesis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2005; 100:40-51; Miller C S, White D K, Royse D D. In situ hybridization analysis of human papillomavirus in orofacial lesions using a consensus biotinylated probe. Am J Dermatopathol 1993; 15:256-9; Yildirim B, Senguven B, Demir C. Prevalence of herpes simplex, Epstein Barr and human papilloma viruses in oral lichen planus. Medicina oral, patologia oral y cirugia bucal 2011; 16:e170-4).
So far, the lack of any study using accurate tools to address the specificity of lesional CTLs in OLP precludes any conclusion about mechanisms underlying this dysregulation of muco-cutaneous T-cell immune responses. Thus, there is need in the art for compositions and methods for diagnosis and treatment of severe erosive OLP.